Frequency and severity of systemic reactions during beta-lactam skin testing in adults with immediate hypersensitivity allergy

Hypersensitivity to beta-lactams (BL) is the most frequent drug allergy, and skin testing (ST) remains the first-line diagnostic tool. Although generally safe, systemic reactions (SR) during ST are a concern. We conducted a 7-year ambispective study (2018-2025) including 216 adults with confirmed immediate hypersensitivity reactions (HSR) to BL, established by positive skin tests (ST) or drug challenge tests (DCT). Among them, 138 (63.9%) had positive ST, predominantly intradermal tests (IDT; 93.5%). Five patients (3.6% of ST-positive; 2.3% of the entire cohort) developed SR during ST, all after IDT following negative skin prick tests (SPT). Reactions were mostly mild (urticaria, generalized pruritus, erythema), although one anaphylaxis occurred. All were rapidly controlled with symptomatic treatment. Surprisingly, all patients with SR had urticaria-angioedema as their index reaction; none had experienced prior anaphylaxis. A significant shorter time interval between the index reaction and allergy evaluation was observed in SR patients (mean 23.6 vs. 48.8 months, p = 0.02). No significant associations were identified for age, sex, culprit BL, or specific IgE. SR during BL ST are infrequent but clinically relevant. SPT appears highly safe, whereas IDT requires particular caution, especially when performed shortly after the index reaction.